The Impact of Some Modulators of the Renin–Angiotensin System on the Scopolamine-Induced Memory Loss Mice Model

As some of the renin–angiotensin–aldosterone system (RAAS)-dependent mechanisms underlying the cognitive performance modulation could include oxidative balance alterations, in this study we aimed to describe some of the potential interactions between RAAS modulators (Losartan and Ramipril) and oxida...

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Main Authors: Daniela-Carmen Ababei, Ioana-Miruna Balmus, Walther Bild, Alin Stelian Ciobica, Radu Marian Lefter, Răzvan-Nicolae Rusu, Gabriela Dumitrita Stanciu, Sabina Cojocaru, Monica Hancianu, Veronica Bild
Format: Article
Language:English
Published: MDPI AG 2023-08-01
Series:Brain Sciences
Subjects:
Online Access:https://www.mdpi.com/2076-3425/13/8/1211
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author Daniela-Carmen Ababei
Ioana-Miruna Balmus
Walther Bild
Alin Stelian Ciobica
Radu Marian Lefter
Răzvan-Nicolae Rusu
Gabriela Dumitrita Stanciu
Sabina Cojocaru
Monica Hancianu
Veronica Bild
author_facet Daniela-Carmen Ababei
Ioana-Miruna Balmus
Walther Bild
Alin Stelian Ciobica
Radu Marian Lefter
Răzvan-Nicolae Rusu
Gabriela Dumitrita Stanciu
Sabina Cojocaru
Monica Hancianu
Veronica Bild
author_sort Daniela-Carmen Ababei
collection DOAJ
description As some of the renin–angiotensin–aldosterone system (RAAS)-dependent mechanisms underlying the cognitive performance modulation could include oxidative balance alterations, in this study we aimed to describe some of the potential interactions between RAAS modulators (Losartan and Ramipril) and oxidative stress in a typical model of memory impairment. In this study, 48 white male Swiss mice were divided into six groups and received RAAS modulators (oral administration Ramipril 4 mg/kg, Losartan 20 mg/kg) and a muscarinic receptors inhibitor (intraperitoneal injection scopolamine, 0.5 mg/kg) for 8 consecutive days. Then, 24 h after the last administration, the animals were euthanized and whole blood and brain tissues were collected. Biological samples were then processed, and biochemical analysis was carried out to assess superoxide dismutase and glutathione activities and malondialdehyde concentrations. In the present experimental conditions, we showed that RAAS modulation via the angiotensin-converting enzyme inhibition (Ramipril) and via the angiotensin II receptor blockage (Losartan) chronic treatments could lead to oxidative stress modulation in a non-selective muscarinic receptors blocker (scopolamine) animal model. Our results showed that Losartan could exhibit a significant systemic antioxidant potential partly preventing the negative oxidative effects of scopolamine and a brain antioxidant potential, mainly by inhibiting the oxidative-stress-mediated cellular damage and apoptosis. Ramipril could also minimize the oxidative-mediated damage to the lipid components of brain tissue resulting from scopolamine administration. Both blood serum and brain changes in oxidative stress status were observed following 8-day treatments with Ramipril, Losartan, scopolamine, and combinations. While the serum oxidative stress modulation observed in this study could suggest the potential effect of RAAS modulation and scopolamine administration on the circulatory system, blood vessels endothelia, and arterial tension modulation, the observed brain tissues oxidative stress modulation could lead to important information on the complex interaction between renin–angiotensin and cholinergic systems.
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spelling doaj.art-46b12a33528f4d40b56bf16a33aad3882023-11-19T00:27:25ZengMDPI AGBrain Sciences2076-34252023-08-01138121110.3390/brainsci13081211The Impact of Some Modulators of the Renin–Angiotensin System on the Scopolamine-Induced Memory Loss Mice ModelDaniela-Carmen Ababei0Ioana-Miruna Balmus1Walther Bild2Alin Stelian Ciobica3Radu Marian Lefter4Răzvan-Nicolae Rusu5Gabriela Dumitrita Stanciu6Sabina Cojocaru7Monica Hancianu8Veronica Bild9Pharmacodynamics and Clinical Pharmacy Department, Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, RomaniaDepartment of Exact Sciences and Natural Sciences, Institute of Interdisciplinary Research, Alexandru Ioan Cuza University, 700506 Iasi, RomaniaCenter of Biomedical Research, Romanian Academy, B dul Carol I, no 8, 700505 Iasi, RomaniaCenter of Biomedical Research, Romanian Academy, B dul Carol I, no 8, 700505 Iasi, RomaniaCenter of Biomedical Research, Romanian Academy, B dul Carol I, no 8, 700505 Iasi, RomaniaPharmacodynamics and Clinical Pharmacy Department, Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, RomaniaAdvanced Research and Development Center for Experimental Medicine (CEMEX), Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, RomaniaDepartment of Biology, Faculty of Biology, Alexandru Ioan Cuza University, 700506 Iasi, RomaniaDepartment of Pharmacognosy, Faculty of Pharmacy, Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, RomaniaPharmacodynamics and Clinical Pharmacy Department, Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, RomaniaAs some of the renin–angiotensin–aldosterone system (RAAS)-dependent mechanisms underlying the cognitive performance modulation could include oxidative balance alterations, in this study we aimed to describe some of the potential interactions between RAAS modulators (Losartan and Ramipril) and oxidative stress in a typical model of memory impairment. In this study, 48 white male Swiss mice were divided into six groups and received RAAS modulators (oral administration Ramipril 4 mg/kg, Losartan 20 mg/kg) and a muscarinic receptors inhibitor (intraperitoneal injection scopolamine, 0.5 mg/kg) for 8 consecutive days. Then, 24 h after the last administration, the animals were euthanized and whole blood and brain tissues were collected. Biological samples were then processed, and biochemical analysis was carried out to assess superoxide dismutase and glutathione activities and malondialdehyde concentrations. In the present experimental conditions, we showed that RAAS modulation via the angiotensin-converting enzyme inhibition (Ramipril) and via the angiotensin II receptor blockage (Losartan) chronic treatments could lead to oxidative stress modulation in a non-selective muscarinic receptors blocker (scopolamine) animal model. Our results showed that Losartan could exhibit a significant systemic antioxidant potential partly preventing the negative oxidative effects of scopolamine and a brain antioxidant potential, mainly by inhibiting the oxidative-stress-mediated cellular damage and apoptosis. Ramipril could also minimize the oxidative-mediated damage to the lipid components of brain tissue resulting from scopolamine administration. Both blood serum and brain changes in oxidative stress status were observed following 8-day treatments with Ramipril, Losartan, scopolamine, and combinations. While the serum oxidative stress modulation observed in this study could suggest the potential effect of RAAS modulation and scopolamine administration on the circulatory system, blood vessels endothelia, and arterial tension modulation, the observed brain tissues oxidative stress modulation could lead to important information on the complex interaction between renin–angiotensin and cholinergic systems.https://www.mdpi.com/2076-3425/13/8/1211RAAScognitive functionsoxidative stressRamiprilLosartanscopolamine
spellingShingle Daniela-Carmen Ababei
Ioana-Miruna Balmus
Walther Bild
Alin Stelian Ciobica
Radu Marian Lefter
Răzvan-Nicolae Rusu
Gabriela Dumitrita Stanciu
Sabina Cojocaru
Monica Hancianu
Veronica Bild
The Impact of Some Modulators of the Renin–Angiotensin System on the Scopolamine-Induced Memory Loss Mice Model
Brain Sciences
RAAS
cognitive functions
oxidative stress
Ramipril
Losartan
scopolamine
title The Impact of Some Modulators of the Renin–Angiotensin System on the Scopolamine-Induced Memory Loss Mice Model
title_full The Impact of Some Modulators of the Renin–Angiotensin System on the Scopolamine-Induced Memory Loss Mice Model
title_fullStr The Impact of Some Modulators of the Renin–Angiotensin System on the Scopolamine-Induced Memory Loss Mice Model
title_full_unstemmed The Impact of Some Modulators of the Renin–Angiotensin System on the Scopolamine-Induced Memory Loss Mice Model
title_short The Impact of Some Modulators of the Renin–Angiotensin System on the Scopolamine-Induced Memory Loss Mice Model
title_sort impact of some modulators of the renin angiotensin system on the scopolamine induced memory loss mice model
topic RAAS
cognitive functions
oxidative stress
Ramipril
Losartan
scopolamine
url https://www.mdpi.com/2076-3425/13/8/1211
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